HIF-1 signaling: an emerging mechanism for mitochondrial dynamics

ABSTRACT

A growing emphasis has been paid to the function of mitochondria in tumors, neurodegenerative disorders (NDs), and cardiovascular diseases. Mitochondria are oxygen-sensitive organelles whose function depends on their structural basis. Mitochondrial dynamics are critical in regulating the structure. Mitochondrial dynamics include fission, fusion, motility, cristae remodeling, and mitophagy. These processes could alter mitochondrial morphology, number, as well as distribution, to regulate complicated cellular signaling processes like metabolism. Meanwhile, they also could modulate cell proliferation and apoptosis. The initiation and progression of several diseases, such as tumors, NDs, cardiovascular disease, were all interrelated with mitochondrial dynamics. HIF-1 is a nuclear protein presented as heterodimers, and its transcriptional activity is triggered by hypoxia. It plays an important role in numerous physiological processes including the development of cardiovascular system, immune system, and cartilage. Additionally, it could evoke compensatory responses in cells during hypoxia through upstream and downstream signaling networks. Moreover, the alteration of oxygen level is a pivotal factor to promote mitochondrial dynamics and HIF-1 activation. HIF-1α might be a promising target for modulating mitochondrial dynamics to develop therapeutic approaches for NDs, immunological diseases, and other related diseases. Here, we reviewed the research progress of mitochondrial dynamics and the potential regulatory mechanism of HIF-1 in mitochondrial dynamics. (AU)